Combination Therapy for the Treatment of Bipolar Disorders

This study has been terminated.
(Funding Expiration)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Dr. Keming Gao, University Hospital Case Medical Center
ClinicalTrials.gov Identifier:
NCT00063362
First received: June 25, 2003
Last updated: December 23, 2013
Last verified: December 2013

June 25, 2003
December 23, 2013
February 2002
July 2007   (final data collection date for primary outcome measure)
The Proportion of Patients Who Experience a Marked and Persistent Bimodal Response [ Time Frame: Baseline and Week 28 ] [ Designated as safety issue: No ]

A marked bimodal response is defined by the following three conditions over four consecutive weeks while on triple therapy and after three weeks of ltg:

  1. Montgomery Asberg Depression Rating Scale (MADRS) total score of <= 19
  2. Young Mania Rating Scale (YMRS) total score of <= 12.5
  3. Global Assessment Scale (GAS) score >= 51

The MADRS measures the severity of a subject's depression symptoms with a possible total score ranging from 0 - 60, with higher scores indicating more severe depression.

The YMRS measures the severity of a subject's manic symptoms with a possible total score ranging from 0 - 60, with higher scores indicating more severe mania.

The GAS measures a used to rate subjectively the social, occupational, and psychological functioning of a subject and ranges in score from 0-100, with a higher score indicating better social, occupational, and psychological functioning.

Not Provided
Complete list of historical versions of study NCT00063362 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
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Combination Therapy for the Treatment of Bipolar Disorders
Combination Therapy in Bipolar Rapid Cycling

This study will compare triple and double drug regimens in the treatment of patients with depression, hypomania, or mania.

Early studies have shown lithium to produce a high percentage of satisfactory clinical response in patients with bipolar disorders. These studies, however, do not include lithium-refractory subgroups, such as bipolar II disorder patients. When the wide spectrum of bipolar disorders is considered, the lithium response rate decreases significantly. More broadly effective regimens are needed.

Participants in this study will be randomly assigned to receive either lithium plus divalproex or lithium, divalproex, and lamotrigine for 7 months. Symptoms of depression and mania will be assessed with scales and patient questionnaires.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Bipolar Disorder
  • Drug: Lithium
    Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 milliequivalent /L (mEq/L).
    Other Name: Lithium Carbonate
  • Drug: Lamotrigine
    Patients were assigned in a one to one ratio to adjunctive lamotrigine versus placebo after stratification for illness type (bipolar I versus bipolar II), historical response to lithium (response versus non-response), and length of current exposure to combination treatment with lithium and divalproex (< 2 months versus ≥ 2 months). During Phase 2, patients were continued on the same doses of lithium and divalproex as during the open-label treatment phase and equal capsules of double-blind lamotrigine or matching placebo were gradually added per a structured dosing schedule up to a minimum dose of 150 mg and a maximum dose of 200 mg per day.
    Other Name: Lamictal
  • Drug: Divalproex
    Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL.
    Other Names:
    • Depakote
    • Valproic Acid
  • Drug: Placebo
    Patients were assigned in a one to one ratio to adjunctive lamotrigine versus placebo after stratification for illness type (bipolar I versus bipolar II), historical response to lithium (response versus non-response), and length of current exposure to combination treatment with lithium and divalproex (< 2 months versus ≥ 2 months). During Phase 2, patients were continued on the same doses of lithium and divalproex as during the open-label treatment phase and equal capsules of double-blind lamotrigine or matching placebo were gradually added per a structured dosing schedule up to a minimum dose of 150 mg and a maximum dose of 200 mg per day.
  • Experimental: Lithium + divalproex + lamotrigine
    Interventions:
    • Drug: Lithium
    • Drug: Lamotrigine
    • Drug: Divalproex
  • Placebo Comparator: Lithium + divalproex + placebo
    Interventions:
    • Drug: Lithium
    • Drug: Divalproex
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
49
July 2007
July 2007   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Bipolar I or II Disorder
  • Meet criteria for rapid cycling, defined as four or more episodes over the past 12 months
  • Meet criteria for a major depressive episode

Exclusion Criteria:

  • History of intolerability of lithium, divalproex, or lamotrigine
Both
16 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00063362
R21 MH62650, R21MH062650, DSIR AT-SO
Yes
Dr. Keming Gao, University Hospital Case Medical Center
University Hospital Case Medical Center
National Institute of Mental Health (NIMH)
Principal Investigator: Keming Gao, MD, PhD Case Western Reserve University / University Hospitals of Cleveland
University Hospital Case Medical Center
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP